rs1476046

Variant names:

• chr6-12292988-G-A
• rs1476046
• NM_001955.5:c.233+479G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-12292988-G-A
• chr6-12292988-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001955.5(EDN1):​c.233+479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,158 control chromosomes in the GnomAD database, including 3,958 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3958 hom., cov: 32)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 14 publications found

Genes affected

EDN1 (HGNC:3176): (endothelin 1) This gene encodes a preproprotein that is proteolytically processed to generate a secreted peptide that belongs to the endothelin/sarafotoxin family. This peptide is a potent vasoconstrictor and its cognate receptors are therapeutic targets in the treatment of pulmonary arterial hypertension. Aberrant expression of this gene may promote tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

EDN1 Gene-Disease associations (from GenCC):

• question mark ears, isolated

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• auriculocondylar syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302734 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.233+479G>A		intron_variant	Intron 2 of 4	ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.233+479G>A		intron_variant	Intron 2 of 4	1	NM_001955.5	ENSP00000368683.5
ENSG00000302734	ENST00000789282.1	n.70+18193C>T		intron_variant	Intron 1 of 3
ENSG00000302734	ENST00000789283.1	n.26-2192C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34176 AN: 152040 Hom.: 3960 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34176 AN: 152158 Hom.: 3958 Cov.: 32 AF XY: 0.228 AC XY: 16927 AN XY: 74386

African (AFR) AF: 0.196 AC: 8122 AN: 41514

American (AMR) AF: 0.227 AC: 3471 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1552 AN: 5182

South Asian (SAS) AF: 0.405 AC: 1952 AN: 4814

European-Finnish (FIN) AF: 0.197 AC: 2082 AN: 10590

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15514 AN: 67984

Other (OTH) AF: 0.205 AC: 434 AN: 2112

Alfa AF: 0.224 Hom.: 641

Bravo AF: 0.220

Asia WGS AF: 0.313 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.72
DANN	Benign	0.65
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1476046; hg19: chr6-12293221;